| OBJECTIVE: Drugs of esters nitrate had been used mostly to physiol coronary artery, to increase nutritional blood flowing to cardiac myocytes and reduce consumption of blood oxygen of cardiac myocytes in clinical treatment traditionally, but as shortter biological half-life , more side effects due to a long-time taking, and lowerring efficacy leading by pile of metabolite, they had some shortcomings In order to maximizea favourable factors and minmize unfavourable ones, a kind of new drug which can provide NO" - 2-(acetylferulamidoethyl) nitrate (Felanite FEL) had been designed and synthetized by the mechanism of cardiovascular effects brought by hydrolysis of efficacious composition of new anti-angina pectoris drug. Recently the methods of treating cornary occlusion embolism had been widely used, such asrthromboly therapy, plastic operation, coronary bypass, intracardiac operation, cardiac transplantation et al. whichcan result in ischemic and reperfused damage, arrhythmia and VF for example. As is well know, VF is one of the primary factors inducing death. The mechanism of physiolling vessol of FEL was reserched by the mothed of decting indentical contract range of smooth muscle and the level of cAMP and cGMP in rat aorta. Meaningwhile ischemic and reperfused model of rats was designed, which can explain the process of di ssolving thrombus after humen encounterring myocardiaJ infarction. For verifing the protection to ischemic and reperfused damage, the effcts of inhibiting apoptosis of FEL were studied, compare with isordnitroglycerin.METHODS: (1)On the basis of the same shrinkage range, vasodilatory effects of nitroglycerin and FEL on rat coronary aorta strips precontracted by noradrenaline and KCl were observed. Effects of FEL on the concentration-reponse curves for noradrenaline and KCl in rat aorta were analyzed. Effects of various vasodilators on level of cAMP and cGMP in rat aorta precontracted with noradrenaline were determined. (2) I schemic and reperfused model of 70 mal adult Wister rat was established by LAD-occlussion. Among them, 30 rats were pre-treated with verapamil, isordil and FEL. apoptotic myocytes were detected with the technique of TUNEL, Bcl-2 and Bax were detected with the method of immunhisochemistry. The apoptosis of cardiac myocytes, Bcl-2 and Bax related genes and influence of verapamil, isordil and FEL were observed.RESULTS: (DLimping vasodilntiry of PEL on rat aorta strips precontracted by noradrenaline (1 mol-L-1) and KC1 (30mmol-L-1) wereproved. It's EC50 were (35.9 3.1) and (36.7 3.1) mol-L-1 successively . and EC50 of nitroglycerin were (18.6 3.8) and (18.1 2.2) mol-L-1successively. Their dependence on concentration were very similar. Vasodilatory effects of the same concentration of them successively weren't significantly different. Both of the concentration-response curves of noradrenaline and KC1 in rat aorta were moved to the rightby AS 30 mol-L-1. And the maximum effects were lowerred. Value of pD2were (3.86 0.06) and (3.98 0.10) successively. The levels of cGMP in rat aorta precontracted with noradrenaline were rised by effects of vasodilators of FEL(P<0. 01). (2)Apoptotic myocytes were not increased in simulated operation group and ischemia-only group(P>0.05), but significantly increased in ischemic and reperfused group(P<0.01),the amount of apoptotic myocytes may be reduced by treatment verapamil, nitroglycerin and FEL before ischemia(P<0. 01). The expression of Bcl-2 and Bax were increased in ischemic, reperfused and pretreatment groups.CONCLUSION: (1) FEL was neither typical Ca2+ inhibitor, nor competitive a -receiter. It's mechanism to physiol coronary artery was similar as nitroglycerin's. Both of them was: supplying extermal NO" and raising the levels of cGMP in smooth muscle. (2)Apoptosis of cardfiac myocytes were observe after ischemic and reperfused. The process can be accelerate by perfusion and inhibited by pre-treatmentwith verapaini1, isordil and FHL The expression of Bcl-2 and Bax were increased by ischem...
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